No 6 (2021)

Cover Page

Articles

Current hygienic aspects of nanotoxicology: theoretical foundations, identification of health hazards and ways to reduce it

Article E.

Abstract

20–21 октября 2021 года в г. Екатеринбурге состоялась II Всероссийская научно-практическая очно-заочная конференция с международным участием «Актуальные гигиенические аспекты  нанотоксикологии: теоретические основы, идентификация опасности для здоровья и пути её снижения» в соответствии с приказом Федеральной службы о надзору в сфере защиты прав потребителей и благополучия человека.

Toxicological Review. 2021;29(6):4-4
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Reviews

Methodological foundations for substantiating safe levels of exposure to artificial nanomaterials (for example, carbon nanotubes) (literature review)

Timerbulatova G.A., Fatkhutdinova L.M.

Abstract

Introduction. The unique physicochemical properties of carbon nanotubes allow them to be used in many fields. The global nanomaterials market is growing every year. An important step in introducing products to the domestic and world markets is to determine the safe exposure levels of CNTs. Establishing a corporate standard can serve as a preliminary stage before the approval of a state hygiene standard. 

Material and methods. The material for the analysis was the sources of information on the available standards for the content of CNTs in the air of the working area using information from regulatory agencies, research centers, CNT manufacturers, bibliographic and abstract databases Web of Science, Scopus, PubMed, RSCI.

Results. A scheme for justifying safe levels of exposure to CNTs (corporate standard) has been developed, consisting of several stages: characterization of CNTs in the air at workplaces, selection of experimental doses of CNTs, preparation of CNT dispersions, and conducting toxicological and hygienic experiments. Justification of the corporate standard is carried out in in vitro and in vivo experiments. The planning of experiments should be carried out taking into account the target organ under the influence of CNT — the respiratory system. The recommended dose / concentration range for experiments should include doses / concentrations derived from calculated and literature data. A necessary step is to obtain homogeneous dispersions in which CNTs become bioavailable for biological systems. In vitro and in vivo experiments determine the level of exposure at which no harmful effect is observed and / or the lowest level of exposure at which there is a harmful effect on the cell culture / respiratory tract of animals. After the stage of substantiating the corporate standard, the enterprise should take measures for several years to adjust the corporate standard based on data from clinical and hygienic studies, during which the working conditions and health status of workers are monitored, and extended toxicological and hygienic studies. 

Conclusion. The presence of a corporate standard will allow the manufacturer of CNTs to carry out activities for the development and implementation of a production control program with the introduction of monitoring the air condition in the working area. The development of a corporate regulation can be seen as a preparatory stage before the establishment of a government regulation.

Toxicological Review. 2021;29(6):5-15
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Principles for assessing the genotoxicity of carbon nanomaterials in vitro (on the example of carbon nanotubes) (literature review)

Gabidinova G.F., Timerbulatova G.A., Fatkhutdinova L.M.

Abstract

Introduction. Genotoxicity of nanomaterials (NM) is becoming a major concern when investigating new NM for their safety. Each mutagen is considered to be potentially carcinogenic, therefore a genotoxicity assessment is necessary. However, a clear strategy for assessing the genotoxic effect of NM has not yet been developed.

Material and methods. The material for the analysis have included literature sources from the bibliographic databases PubMed, Scopus, RSCI.

Results. Physicochemical characterization of NM is carried out using high-resolution microscopic and light scattering methods. Before testing for genotoxicity, it is necessary to know the cytotoxicity of the tested NM in order to select the appropriate concentration range. The most important and significant tests are based on the cell viability. MTT assay is a colorimetric test that evaluates the metabolic activity of cells. In addition, viability can be determined using microscopy, flow cytometry, determination of lactate dehydrogenase. Genotoxicity evaluation can be carried out only after the preliminary steps. The strategy should include genotoxicity endpoints: DNA damage, gene mutations, chromosomal damage. The in vitro mammalian gene mutation test, usually performed using mouse lymphoma cells, detects a wide range of genetic damage, including gene deletions. The most common test for detecting chromosomal damage is an in vitro micronucleus assay. DNA strand breaks are most often assessed using the comet DNA assay.

Conclusion. Compulsory stages in the study of the genotoxicity of nanomaterials should be preliminary studies, including physicochemical characterization and assessment of cytotoxicity, as well as the study of the endpoints of genotoxicity and potential mechanisms.

Toxicological Review. 2021;29(6):16-23
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Original articles

Characteristics of atmospheric air pollution by fine particles based on regional monitoring data

Fatkhutdinova L.M., Timerbulatova G.A., Bocharov E.P., Sizova E.P., Gabidinova G.F., Yapparova L.I., Vasilev E.S., Sharifullin R.L., Zaripov S.K., Zalyalov R.R.

Abstract

Introduction. Air pollution with particulate matter (PM) is a serious global problem. In the Russian Federation, regular field measurements of PMs in the ambient air are carried out only in a few cities, and the data, as a rule, are not systematized. Aim of the study: long-term analysis of the data set on concentrations of fine particles in the ambient air of the city of Kazan.

Material and methods. Long-term analysis of ambient air pollution by fine particles in the city of Kazan for the period from 2016 to 2020 has been carried out. To study the effect of separate factors (year, measurement time during the day, climatic conditions, the presence of other pollutants) on the levels of PM10 and PM2.5, regression analysis was applied based on the method of mixed models. To characterize the elemental composition of the PM2.5 fraction, sampling of atmospheric air on PVC filters was carried out by use of 100 NR impactor (TSI, USA). The step function and MPPD model were applied to calculate the number of particles and the mass of the deposited fraction of fine particulate matter in different regions of the human respiratory tract.

Results. The PM10 concentrations remained stable over a 5-year period, while the PM2.5 concentrations decreased. At the same time, an increase in the maximum annual concentrations of both fractions was observed. The concentrations of PM10 and PM2.5 significantly depended on climatic conditions. The presence of nitrogen oxides and organic carbon in the ambient air was significantly associated with higher concentrations of PM10 and PM2.5. The elemental composition of PM2.5 fraction was represented mainly by carbon (C) (from 86.16% to 93.45%). Mathematical modeling has shown that PM10 is mainly deposited in the upper respiratory tract, and their presence in the tracheobronchial and alveolar zones is insignificant. PM2.5 particles reach the lower respiratory tract and alveolar area. 

Conclusion. A statistically significant upward long-term trend in the maximum annual ambient concentrations for both fractions of fine particles can increase health risks. Secondary pollutants (nitrogen oxides, organic carbon) are important factors for the formation of secondary particles in the ambient air. The results obtained indicate that when assessing the risks to public health, it is necessary not only to use the concentrations of fine particles in ambient air, but also to consider the degree of deposition of separate fractions in different parts of the human respiratory tract, considering the alleged pathogenesis and priority target cells characteristic of individual diseases.

Toxicological Review. 2021;29(6):24-32
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Effects of long-term oral administration of silver nanoparticles on the cognitive functions of mammals

Antsiferova A.A., Kopaeva M.Y., Kochkin V.N., Kashkarov P.K.

Abstract

Introduction. Since the beginning of the XXI century, silver nanoparticles have been widely used in various industries, medicine and pharmaceuticals due to their pronounced antibacterial, antiviral and fungicidal properties. In connection with such a high demand for the use of silver nanoparticles, it is very important to understand the associated potential risks from their use.

Materials and methods. In the course of the work, there has been a study of the effects of the long-term oral administration of a commercially produced dietary supplement based on silver nanoparticles with a size of 34 nm and stabilized with polyvinylpyrrolidone in an amount of 50 μg/day/animal on the cognitive functions of C57Bl/6 mice, as well as their accumulation in the brain by the method of instrumental neutron activation analysis. The dietary supplement used is recommended for people as a treatment for gastrointestinal infections. 

Results. It was found that after 180 days of administration, silver nanoparticles impair long-term contextual memory, and over time, the content of silver in the brain increases.

Conclusion. Presumably impaired cognitive function with accumulation of silver in the brains of mice. This poses the risk of prolonged oral use of the silver nanoparticles.

Toxicological Review. 2021;29(6):33-38
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Comparative assessment of the pulmonary effect in rats to a single intratracheal administration of selenium or copper oxide nanoparticles

Sutunkova M.P., Privalova L.I., Ryabova Y.V., Minigalieva I.A., Tazhigulova A.V., Labzova A.K., Klinova S.V., Solovyeva S.N., Chernyshov I.N., Minigalieva R.F., Katsnelson B.A.

Abstract

Introduction. Professional contact with selenium, copper and their compounds, including nanoscale forms, occurs in the metallurgical processes of copper sludge processing, copper pyrite roasting, manganese, selenium and tellurium production. The wide prevalence of selenium and copper oxide nanoparticles (SeO and CuO NPs) necessitates a comparative experimental assessment of its toxicity.

Materials and methods. The copper or selenium oxide nanoparticle suspensions or a deionized water were intratracheally administered to female rats at single time. The bronchoalveolar lavage fluid (BALF) was obtained 24 hours after administration. There were evaluated the cellular composition and the biochemical parameters of the BALF. 

Results. The changes in the cellular composition of BALF demonstrate the SeO-NP and CuO-NP have a cytotoxic effect. The BALF biochemical indices were changed to a greater extent under CuO-NP. However, the phagocytic capacity of alveolar macrophages is activated under the SeO-NP.

Conclusion. The SeO-NP and CuO-NP have a cytotoxic effect. SeO-NP have a positive effect on pulmonary phagocytosis, which can presumably be associated with selenium is a biomicroelement.

Toxicological Review. 2021;29(6):39-46
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Features of bioaccumulation and toxic effects of copper (II) oxide nanoparticles under the oral route of intake into the body

Zemlyanova M.A., Stepankov M.S., Ignatova A.M.

Abstract

Introduction. Active use in various spheres of economic activity and the large-scale nature of production determine the relevance of studying the effects of copper (II) oxide nanoparticles (CuO NPs) on the body during the oral route of intake.

Material and methods. Particle size was determined by scanning electron microscopy and dynamic laser light scattering; specific surface area — Brunauer, Emmett and Teller; total pore volume — Barrett, Joyner and Khalenda. Acute oral toxicity of CuO NPs was studied in Wistar rats in accordance with GOST 32644-2014, multiple oral toxicity was studied by the Lim method. After repeated exposure, the biochemical and hematological parameters of the blood, the concentration of copper in the organs, and pathomorphological changes in the tissues of the organs were determined.

Results. The size of CuO NPs in the composition of the native powder was 45.86 nm, in the aqueous suspension — 307.40 nm, the specific surface area was 17.70 m2/g, and the total pore volume was 0.056 cm3/g. According to the results of a single oral exposure, the LD50 value was > 2000 mg / kg body weight, which corresponds to 3 (GOST 12.1.007-76) and 4 (GOST 32644-2014) hazard classes. With repeated oral exposure, an increase in the levels of activity of ALT, AST, ALP, LDH, amylase, AOA and MDA was noted; the relative number of segmented neutrophils is increased, the number of leukocytes is increased, the relative number of lymphocytes is reduced. The concentration of copper under the action of NPs increases in the lungs, liver, stomach, intestines, kidneys, brain and blood. Pathomorphological changes in the tissues of the liver, kidneys, stomach, small and large intestines and lungs were established.

Conclusion. The results obtained prove the presence of toxic properties of CuO NPs and can be used in the development of preventive measures for workers and consumers in contact with products containing CuO NPs.

Toxicological Review. 2021;29(6):47-53
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Comparison of toxic effects of iron-molybdenum polyoxometalates and mixture of their components

Gette I.F., Ostroushko A.A., Danilova I.G., Tonkushina M.O.

Abstract

Introduction. The physicochemical properties and the impact on living organisms of nanoparticles and components that make up nanoparticles may differ radically, however, insufficient attention is paid to a comparative study of the toxicity of nanoparticles and constituents of nanoparticles.

Material and methods. Biochemical and hematological parameters in the blood of 50 male Wistar rats were determined after a single, seven-fold and thirty-fold intramuscular injection of an aqueous solution of iron-molybdenum nanocluster polyoxometalates (POM) and a mixture of the POM components at a dose of 1.5 mg/kg. A solution of a POM components’ mixture was obtained by the destruction of POM with an increase in pH, followed by neutralization, since POM are unstable in an alkaline medium.

Results. The introduction of POM did not cause deviations from the norm in the activity of AST, ALT, total alkaline phosphatase and its bone isoenzyme, α-amylase, protein content, urea and creatinine, which indicates the absence of cytolytic syndrome, including in the liver and myocardium, no damage to the acinar part of pancreas, changes in bone tissue, preservation of the protein-synthetic function of the liver and the filtering ability of the kidneys. The introduction of a solution of POM components (molybdenum, iron) was accompanied by an increase in the activity of AST, alkaline phosphatase, the AST / ALT ratio after 7 injections and an increase in the last two parameters after 30 injections. The impact of POM is characterized by an increase in the content of hemoglobin and erythrocytes in the blood and less pronounced leukopenia, in contrast to the mixture of POM components.

Conclusion. A less pronounced deviation from the norm of biochemical parameters and a lower degree of leukopenia make it possible to assess the effect of POM nanoparticles as less toxic than the action of POM components not organized into nanoparticles.

Toxicological Review. 2021;29(6):54-59
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Effect of copper oxide nanoparticles on gene expression of NMDA receptor

Sitnikov I.A., Shaikhova D.R., Amromina A.M., Sutunkova M.P., Ryabova Y.V., Tazhigulova A.V., Ruzakov V.O.

Abstract

Introduction. Copper plays an important role in the metabolism of the brain, but particles of copper, in the nanometer range, exhibit neurotoxic properties and cause malfunctioning of brain cells.

Material and methods. For 6 weeks, 3 times a week, the animals were injected with a suspension of NPs of copper oxide. The determination of the expression of the genes GRIN1, GRIN2a, and GRIN2b, encoding the proteins GluN1, GluN2a, and GluN2b, respectively, was carried out by real-time PCR with probes.

Results. A statistically significant decrease in the expression level of genes encoding NMDA receptor proteins was determined when exposed to 0.5 mg/ml CuO nanoparticles (ΔCt(GRIN1) = 0.813; ΔCt(GRIN2A) = 3.477; ΔCt(GRIN2B) = 1.37) in comparison with control group (ΔCt(GRIN1) = 6.301; ΔCt(GRIN2A) = 7.823; ΔCt(GRIN2B) = 4.747).

Conclusion. Evaluation of gene expression of the NMDA receptor may be present in a genetic marker to determine the toxic effect of copper oxide nanoparticles; however, further studies are needed, including behavioral tests to confirm the clinical manifestations of neurodegenerative disorders.

Toxicological Review. 2021;29(6):60-66
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Index of articles

Index of articles published in the journal "Toksikologicheskiy vestnik (Toxicological Review)" in 2021

Редакция E.

Abstract

 Указатель статей, опубликованных в журнале «Токсикологический вестник» в 2021 году 

Toxicological Review. 2021;29(6):67-68
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